The main goal of the proposed research is the identification of genotypes of the fruitfly, Drosophila melanogaster, that are genetically superior in learning or memory. The long-term goal of this research is mapping and eventually cloning loci that increase learning or memory. This approach contrasts with all previous "genetic dissections" of learning and memory in Drosophila, which identify genes correlated with deficits in learning or memory, because it focuses on the identification of gene loci that correlate with increased learning or memory rates (in comparison with a control genotype). Such loci that produce better learning or memory are far more likely to be causally related to the biochemical mechanisms of learning and memory than are loci that may have deleterious (and potentially non-specific) effects on learning or memory via disruption of cell metabolism. The principal method of isolating genotypes of superior learning or memory capabilities will be by means of artificial selection for increased learning or memory in classical and operant conditioning paradigms. A second major goal of the proposed research is a critical test of the biochemical model of learning and memory developed for the marine mollusk, Aplysia, using individually- tested D. melanogaster. This test is important because two of the key enzymes in the Aplysia model are identical to those coded for by gene loci in Drosophila that have been correlated with mutations that my decrease learning or memory. This research on the genetic causes of individual differences in learning and memory will be of significant value in understanding how the biochemistry of learning or memory can be perturbed by mutations or by environmental agents to produce deficits in learning or memory in human subjects. This research is thus relevant to a number of human conditions, such as developmental disabilities, learning disorders and diseases of memory (such as Alzheimer's disease).